A major difficulty in accepting hepatic microsomal cytochrome P-450 as a site for the reduction of drugs in vivo is the concept that is acts as a mixed-function oxidase and a reductase under the same physiological conditions, particularly since in vitro oxygen inhibits cytochrome P-450 dependent reductions. We propose that in vivo cytochrome P-450 is an important site for the reduction of at least two classes of compounds, tertiary amine N-oxides and halogenated hydrocarbons, and that different forms of cytochrome P-450 catalyze oxidative and reductive reactions. The form(s) of cytochrome P-450 catalyzing reduction would be expected to exhibit a lower affinity for oxygen. Evidence is presented to support our suggestion of different forms of cytochrome p-450; the different affinity of oxygen for microsomal cytochrome P-450 and as an inhibitor of reduction, the ability of NADH to support reduction but not oxidative metabolism and the selective destruction of some forms of cytochrome P-450 during anaerobic halothane metabolism. We propose to isolate different forms of cytochrome P-450 in high yield from control and induced rats and to study the ability of reconstituted systems of purified cytochrome P-450 and the other components of the microsomal drug metabolizing system to reduce indicine N-oxide and halothane. The ability of NADH and NADPH to act as a source of reducing equivalents and the oxygen sensitivity of the system will receive special emphasis. Monoclonal antibodies specific for a single antigenic determinant site will be prepared against all of the components of the microsomal drug metabolizing system by the cell fusion technique employing hybridized antibody secreting cells in culture. The substrates chosen for study, indicine N-oxide, an anticancer drug, and halothane, an inhalational anesthetic, are compounds whose therapeutic usefulness is implicated by reduction to potentially hepatotoxic metabolites.